Infarct stabilization and cardiac repair with a VEGF-conjugated, injectable hydrogel.

Abstract

Injectable scaffolds made of biodegradable biomaterials can stabilize a myocardial infarct and promote cardiac repair. Here, we describe the synthesis of a new, temperature-sensitive, aliphatic polyester hydrogel (HG) conjugated with vascular endothelial growth factor (VEGF) and evaluate its effects on cardiac recovery after a myocardial infarction (MI). Seven days after coronary ligation in rats, PBS, HG, or HG mixed or conjugated with VEGF (HG + VEGF or HG-VEGF, respectively) was injected around the infarct (n = 8-11/group). Function was evaluated by echocardiography at multiple time points. Pressure-volume measurements were taken and infarct morphometry and blood vessel density were assessed at 35 days after injection. HG-VEGF provided localized, sustained VEGF function. Compared with outcomes in the PBS group, fractional shortening, ventricular volumes, preload recruitable stroke work, and end-systolic elastance were all preserved (p < 0.05) in the HG and HG + VEGF groups, and further preserved in the HG-VEGF group. Conjugated VEGF also produced the highest blood vessel density (p < 0.05). The infarct thinned and dilated after PBS injection, but was smaller and thicker in hearts treated with HG (p < 0.05). Our temperature-sensitive HG attenuated adverse cardiac remodeling and improved ventricular function when injected after an MI. VEGF delivery enhanced these effects when the VEGF was conjugated to the HG.